This proposal is: 1) for preparation of various corticosteroid conjugates of nucleoside antitumor agents linked through a phosphodiester bond in an effort to improve their therapeutic index in the treatment of malignant tumors, 2) for performance of preliminary evaluation of the conjugates in experimental animal tumor models. In the preliminary evaluation of antitumor activity against L1210 im mice, the ara-C conjugates of cortisol, cortisone, prednisolone, prednisone and corticosterone have been found to be superior to the combination of ara-C and the steroid and to ara-C alone at the optimal dose level. Thus, more of the corticosteroid conjugates of ara-C, 5-fluorodeoxyuridine, 5-azacytidine, arabinosyladenine, 6-mercaptopurine ribonucleoside and tubercidin will be synthesized by: 1) a condensation of the steroid with the properly protected 5'-nucleotide in the presence of N,N'-dicyclohexylcarbodiimide or other condensing agents; 2) a direct route from a reaction of the nucleoside and POC13 followed by reacting the steroid. The conjugates will be tested against L1210 lymphoid leukemia in culture as well as ip and ic implanted L1210 in mice. The conjugates will be further tested in other animal tumor models available in our Institute. The enzymatic cleavage of the phosphodiester bond and resistance to cytidine deaminase will be studied. After the LD50 in mice of the active compounds has been determined, they will be sent to the National Cancer Institute for further testing in routine animal cancer models.